title: Interleukin-6 is not expressed in activated microglia and in reactive astrocytes in response to lesion of rat basal forebrain cholinergic system as demonstrated by combined in situ hybridization and immunocytochemistry.
abstract: Interleukin-6 may play an essential role in early inflammatory processes as response to degenerating cholinergic cells in the nucleus basalis of Meynert in patients suffering Alzheimer's disease. The cholinergic immunotoxin, 192IgG-saporin, was applied to produce selective and specific degenerations of basal forebrain cholinergic cells. To disclose the lesion-induced temporal cascade of the expression pattern of IL-6, and to reveal the cellular source for production and secretion of IL-6 in vivo after endogeneously induced basal forebrain cholinergic cell loss, both in situ hybridization and immunocytochemistry for IL-6 were performed. To identify the cell types expressing IL-6 mRNA, double labeling techniques were applied combining in situ hybridization technique with immunocytochemistry and lectin histochemistry for both micro- and astroglia and a number of neuronal markers including choline acetyltransferase, parvalbumin, and neurofilaments. In the intact brain, IL-6 is mainly localized in neurons, in particular in both cholinergic and GABAergic neurons of the basal forebrain. Although basal forebrain cholinergic lesion resulted in a dramatic increase in the number of micro- and astroglial cells at the lesion site, IL-6 expression could not be detected in any of the lesion-induced activated glial cell types. Moreover, cholinergic lesion led to a reduced number of IL-6-expressing cells in the basal forebrain, which is assumed to be due to the loss of cholinergic cells. The predominantly neuronal localization in rat brain suggests a role for IL-6 in activating micro- and astroglial cells in response to degenerating cholinergic neurons.
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Medical Faculty, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Lemke
authors.forename: W
authors.initials: W
authors.lastname: Härtig
authors.forename: S
authors.initials: S
authors.lastname: Rossner
authors.forename: V
authors.initials: V
authors.lastname: Bigl
authors.forename: R
authors.initials: R
authors.lastname: Schliebs
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D000918:Antibody Specificity; D001253:Astrocytes / Q000378:metabolism*; D001479:Basal Ganglia / Q000166:cytology / Q000502:physiology*; D018678:Cholinergic Agents / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000633:toxicity; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D005904:Glial Fibrillary Acidic Protein; D000922:Immunotoxins; D015850:Interleukin-6; D012333:RNA, Messenger; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins